BACKGROUND: The candidate malaria vaccine RTS,S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules. We conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS,S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of ≥37.5°C and infection with Plasmodium falciparum of >2,500 parasites per cubic millimeter). ...

A three-dose vaccination with the malaria vaccine candidate RTS,S/AS01 initially protected African children against the disease, but its efficacy significantly diminished during a 7-year follow-up period, researchers reported in the New England Journal of Medicine.

“We found that RTS,S/AS01 provided efficacy in the first year after vaccination but that the efficacy subsequently waned,” Ally Olotu, PhD, of the Kenya Medical Research Institute, Wellcome Trust Program, and colleagues wrote. “Efficacy was close to zero in the fourth year and may have been negative in the fifth year.”

In the double blind, randomized, controlled, phase 2 trial, children from Kilifi, Kenya, and Korogwe, Tanzania, were assigned RTS,S/AS01 (GlaxoSmithKline Biologicals/PATH Malaria Vaccine Initiative; n = 223) or a rabies vaccine as the control (n = 224). Children were aged 5 to 17 months at first vaccination; the second dose was administered 1 month after the initial vaccination, and the third dose came at 2 months after baseline.

During the 7-year follow-up, the researchers reported 1,002 episodes of malaria among the RTS,S/AS01 group, and 992 events among controls. Overall efficacy in the intention-to-treat cohort across 7 years was 4.4% (95% CI, –17 to 21.9), which the investigators described as “substantially lower than that seen over short-term follow-up.” The vaccine’s efficacy was 35.9% in the first year and dropped to 2.5% in the fourth year.

Efficacy was lower, Olotu and colleagues wrote, among children who lived in areas with higher exposure to malarial parasites (–2.4%; 95% CI, –26.1 to 16.8) vs. those living in the low-exposure cohort (16.6%; 95% CI, –24.6 to 44.2).

“In areas with a high intensity of malaria-parasite transmission, some of the early gains in averting the malaria burden can be lost in later years owing to a waning in vaccine efficacy,” Olotu and colleagues wrote. “It will be essential to monitor efficacy in longer-term follow-up for year 5 and beyond to accurately measure the benefit and potential risk of vaccination with the RTS,S/AS01 vaccine.” – by Andy Polhamus

Disclosure: Olotu reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.